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J Ethn Foods 4 (2017) 236e241

Contents lists available at ScienceDirect

Journal of Ethnic Foods


journal homepage: http://journalofethnicfoods.net

Review Article

Ethnic and paleolithic diet: Where do they stand in inflammation


alleviation? A discussion
Seema Patel a, *, Hafiz A.R. Suleria b, c
a
Bioinformatics and Medical Informatics Research Center, San Diego State University, San Diego, CA, USA
b
UQ Diamantina Institute, Translational Research Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
c
Department of Food, Nutrition, Dietetics & Health, Kansas State University, Manhattan, KS, USA

a r t i c l e i n f o a b s t r a c t

Article history: The current food options, especially in the Western countries, are acidogenic, which reduce extracellular
Received 26 July 2017 pH and perturb ionic homeostasis. The acidity-activated enzymes mediate a large panel of chronic and
Received in revised form acute diseases.
10 October 2017
To quell the morbidities and mortalities associated with the metabolic syndromes, nonpharmacologic
Accepted 11 October 2017
Available online 16 October 2017
approaches are preferred. Dietary interventions are critical in this regard. Among the array of dietary
patterns, paleo diet has garnered much attention in the last decade. This diet rich in phytochemicals and
unsaturated fatty acids is deemed wholesome for the body. Several studies have proven this claim, yet
Keywords:
Homeostasis their nutritional adequacy for all age groups is contentious. The popularity of ethnic foods is rising; but
Inflammation their nutrition and safety position can vary. Although some of them are close to paleo food, some are
Metabolic acidosis unhealthy. This review explores the mechanism by which paleo diet restores homeostasis of the body
Paleo diet and how its inherent nutritional deficiency can be amended with conventional diet, by the formulation
Western diet of personalized diet. This compilation is expected to be insightful for dietary optimization.
© 2017 Korea Food Research Institute. Published by Elsevier B.V. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction civilization, food paradigms changed drastically. With


agriculture and animal domestication (Neolithic Revolution), diet
Paleolithic diet or paleo diet, the food habits of humans during was dominated by grains and dairy products. It tilted the extra-
the Paleolithic Era (45,000e40,000 to 10,000 BC) has got immense cellular fluid neutrality towards acidity [5]. But, industrialization
popularity in recent times, in keeping with the rising instances of (Industrial Revolution) and the emergence of processed food
inflammatory diseases, autoimmune pathologies, and cancers. A crossed the tipping point [5]. Increment in the consumption of
paleo diet is a modern dietary regimen based on foods presumably processed foods, together with a reduction in fruit and vegetable
eaten regularly during the Paleolithic Era, which includes lean intake, has dramatically changed the pattern [6]. The processed,
meat, fish, shellfish, fruits, vegetables, roots, eggs, and nuts, but not high-carbohydrate, and high-fat diet increased the extracellular
grains, dairy products, salt, or refined fats and sugar [1], which acidity, activated the zymogens, and inflamed the system [7]. No
became staple food long after the appearance of fully modern wonder, in current times, metabolic, autoimmune, endocrine, and
humans [2]. While some believe that paleo diet is indeed health neural diseases abound in mankind, especially in the developed
promoting, some dismiss it as “hype” or “fad” [3]. However, current regions of the world [8]. Ignorance of this culprit, combined with
evaluations have supported that this diet is compatible for health, easy accessibility of drugs, is imposing further oxidative stress on
and it should be made a staple in food platter. The explanation is the body [9,10] and skewing the pH toward more acidic. The
that the human body has evolved to its current state because of phenotype of the modern human might have become refined
nourishment by fruits, tubers, nuts, etc. [4]. Paleolithic diet was today, but the genome is almost the same since the Paleolithic Era
alkalogenic; therefore, it kept human extracellular fluid pH neutral, [11,12]. While the genome is static, the food habit has undergone
a requisite for homeostasis. However, with the progress of radical change, which is taking toll on the mankind.
In realization of the adverse effects of changed food habits, there
is a revival in interest for ethnic foods. Cajun cuisine which includes
* Corresponding author. Bioinformatics and Medical Informatics Research Center,
dish such as gumbo, jambalaya, and boiled crawfish are popular
San Diego State University, 5500 Campanile Dr, San Diego, CA 92182, USA.
E-mail address: seemabiotech83@gmail.com (S. Patel).
across the United States [13]. In Bedouin Arab minority

https://doi.org/10.1016/j.jef.2017.10.004
2352-6181/© 2017 Korea Food Research Institute. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).
S. Patel, H.A.R. Suleria / Paleolithic diet to prevent inflammation and acidosis 237

communities, ethnic foods include za'atar, leafy dark green vege- Whatever was abundant or easily obtained dominated as ethnic
tables, and camel milk [14]. Japanese ethnic dishes include fish and food. Food scarcity has led to the invention of different strategies to
seaweed. Corn and flour tortillas, beans, tomatoes, chili peppers, deal with antinutrients and to make the most of the available
lard, and beef tallow are cooking mainstays of Mexican foods. materials. Before agriculture succeeded and globalization improved
Medical nutrition therapy is considered for the management of the food scenario, people in different countries had to deal with
pathologies like end-stage kidney disease [15]. Diet therapy is the drought and famine, which often compelled them to integrate odd
cornerstone of gestational diabetes mellitus. things to their food platter. Therefore, what may come across as
At the same time, the question of how ethnic dietary preference delicious for a particular culture might appear gross to the other.
may be influencing diseases is coming forth. Not all ethnic foods are “Huitlacoche,” the Ustilago maydis e caused fungal gall on corn cobs
healthy in terms of their ingredients or processing technique. (Zea mays L.), was a delicacy in Aztec cuisine and is relished in Latin
Polyunsaturated and monounsaturated fatty acids were found America [22]. Obesity or a particular disease is pervasive in a cul-
higher in most ethnic foods consumed in Italy and Spain compared ture because of the dominance of particular ingredients in the
with ethnic foods of other countries [16]. Ethnic and cultural factors cuisine. Native American tribes living in harsh conditions subsisted
determine dietary preferences. As globalization spreads across the on various plant and animal products, for their nutritional needs.
world, societies are becoming multicultural and people are Kutzadika people in Mono Lake region consumed alkali fly (Ephydra
showing keen interest to taste the ethnic foods from different hians) pupae; Paiute Indians consumed Pandora moth (Coloradia
cultures. However, it might be difficult on the metabolism, as the pandora) larvae; the Maidu people consumed carpenter ants
genetics has evolved differently due to distinct dietary patterns. (Camponotus spp.); some tribes used secretions of mealy plum
Salt-loaded seafood might be metabolized in a Japanese person but aphid (Hyalopterus pruni) as sugar. People in the Midwest of the
might cause hypertension in an Indian person. An European person United States used the katydid (Anabrus simplex) as food. In Oriental
might develop allergy to peanuts, while the nut can be a common countries such as Thailand, Vietnam, and Cambodia, people eat
ingredient in Chinese cuisine. Therefore, it is better to stick to one's grasshoppers, crickets, spiders, scorpions, ants, and weevil
own diet. Even one's own ethnic food should be consumed in larvae. Chapulines, the grasshoppers (Sphenarium sp.), are eaten in
moderation, as taste is not the reflection of the nutritional profile or Mexico and Central America [23]. In Japanese culture, wasp, silk
antinutrients in the food. Cassava (Manihot esculenta Crantz) root is moth, cicada, and grasshopper preparations are served in restau-
used as a food source in certain cultures [17]. It contains neurotoxic rants [24]. Casu Marzu, a putrid cheese made from sheep milk has
cyanogenic glycosides linamarin and lotaustralin, which can cause maggots of cheese fly (Piophila casei) [25]. The consumption of bats,
cyanide poisoning [17]. An excitatory amino acid L-ODAP (b-N- frogs, bird egg fetus, and swiftlet bird's nest is prevalent in different
oxalyl-L-a, b-diaminopropionic acid) in Lathyrus sativus (grass pea parts of the world. Tibetans are a high-altitude community, and
or khesari dal), when ingested regularly, can cause paralysis [18,19]. they thrive with limited food resources because of their genes that
An ethnic community, the Chamorro people of Guam, is often adapt to particular low-temperatures (HIF2A/EPAS1 and EGLN1)
afflicted with neurodegenerative disease clusters of Alzheimer's, [26]. Other people exposed to these meager food settings may
Parkinson's, and amyotrophic lateral sclerosis, because of their develop nutritional deficiencies. The Maasai, tribe of Tanzania, are
consumption of cycad (Cycas micronesica) seeds, which contains seminomadic people, and their pastoralist way of living exposes
neurotoxins beta-N-methylamino-L-alanine [20]. The Japanese them to severe food insecurity, though meat, milk, and ugali (a thick
traditional puffer fish (fugu or blowfish) contains tetrodotoxin, maize-based porridge) constitute their primary food [27].
which if consumed can be fatal [21]. Japanese people have learned In current times, people are showing interest for exotic ethnic
to ferment the fish to reduce its toxicity. A bamboo species Phyl- foods. Japan's sushi, Italy's pasta, El Salvador's fried plantains,
lostachys edulis, used as food, contains a-amylase inhibitors such as Afghanistan's kabob, India's curry, Ireland's fish and chips, Ethiopia's
orientin, isoorientin, vitexin, and isovitexin. The leaves are soaked, injera, Vietnam's noodle soup, Hawaii's poke (raw fish salad), and
heat inactivated, and cooked to eliminate the inhibitors. Ethnic Mexico's burrito, which were once ethnic food of a particular region
foods have their origin in the availability of the ingredients. of country are now global fare. Fig. 1 presents some ethnic foods

Fig. 1. Some ethnic foods from different countries. (A) Injera. (B) Kabob. (C) Fried banana. (D) Poke. (E) Biryani. (F) Noodle soup. Some of these ethnic foods are of high calorie, high
protein, and high fat, while some are nutrition poor.
238 J Ethn Foods 2017; 4: 236e241

from different countries. Even, they are showing interest for such products have hormones like prolactin, estrogen, progesterone,
bizarre preparations as part of food tourism and for the sake of androgen, insulin-like growth factor-1, and prostaglandins [44].
tasting exotic foods. However, the risks are not considered. Snake Apart from those, other estrogenic, thyrostatic, and beta-adrenergic
wine, alcohol steeped with venomous snake, is sold in China, compounds are added to these foods, despite regulations [45].
consumption of which had led to cases of coagulopathy [28]. Ar- Spectrometric analyses have identified trace amounts of pesticides
thropods have chitin and tropomyosin which can cause allergy and like alachlor, atrazine, butachlor, isoproturon, malaoxon, methyl
anaphylaxis [29]. Food professionals suspect the hygienic paraoxon, monocrotophos, phorate sulfone, phorate sulfoxide, 2,4-
practice and labeling of the ethnic food preparations. Mycotoxins D, phorate, etc. in popular soft drinks [46]. Unfortunately, the cur-
such as trichothecenes and ochratoxin A are present in chili pow- rent generation is under the grip of these acidogenic and pesticide-
der, curry powder, and ginger [30]. Kidney bean, which is a staple in laced foods [47]. These types of foods are known to be acidogenic, for
Hispanic cuisine, is known to cause allergic incidents in people with they tilt the acidebase balance in favor of acidity [48]. A majority of
different genotypes. This review analyses the pros and cons of the morbidities afflicting mankind today are attributed to the Western
paleo diet. Further, the overlap between ethnic foods and paleo diet. Inflammatory ailments from the acne vulgaris to diabetes,
foods has been discussed. tumorigenesis, sepsis, celiac disease, Crohn's disease, inflammatory
bowel disease, obesity, nonalcoholic fatty liver disease, cardiovas-
Paleolithic diet cular disease, chronic obstructive pulmonary disease, chronic kid-
ney disease, faster bone resorption, brain ischemia, etc. have been
In a 3-month-long randomized crossover study, a paleo diet linked to the unhealthy constituents of the Western acidogenic diet
ingestion improved the glycemic control and several cardiovascular [38,47,49,50].
risk factors in type 2 diabetes patients [1]. In an observational
study, paleo diet reduced the risk of a number of metabolic syn- Mechanisms of amelioration
dromes, as determined from the decline in weight, C-reactive
protein, glycated hemoglobin, improved blood pressure, glucose The healthy aspect of paleo diet stems from its buffer-like effect
tolerance, insulin level, and lipid profiles [5]. Frassetto et al also on the body pH. Ions and electrolyte balance in the body is para-
found that 10 days of a paleo diet improved the diastolic blood mount for survival. None of the living organisms can escape the
pressure, insulin sensitivity, and lipid parameters [31]. Paleolithic fluctuation in pH. The shift in pH ushers in a deluge of undesirable
diet is associated with lower levels of systemic inflammation and consequences. Acidic milieu acts as stressors due to the abundance
oxidative stress in humans, as determined from the low-plasma of reactive oxygen species, reactive nitrogen species, etc. [51]. The
high-sensitivity C-reactive protein and F2-isoprostane level stressors favor the activation of a range of enzymes which ought to
(Whalen et al, 2016). F2-isoprostane is a specific prostaglandin F2- be dormant [52,53]. Proteases (matrix metalloproteases and ca-
like compound, derived from the nonenzymatic peroxidation of thepsins), nitric oxide synthase, adenosine triphosphate synthase,
arachidonic acid. A paleo diet improves fat mass and metabolic glycosidases, urease (Ni2þ-containing hydrolase), phospholipase D,
balance, including insulin sensitivity, glycemic control, and leptin in cyclooxygenase-2, and aromatase are some of the aberrantly acti-
patients with type 2 diabetes [32]. A randomized controlled study vated enzymes which initiate pathologic cascades [54e62]. Acidosis
involving 2 weeks of paleo diet intake could ameliorate metabolic induces mitogen-activated protein kinase phosphorylation, a
syndrome, especially cardiovascular risk factors [33]. A systematic requisite for pathologies [63]. Extracellular acidity activates proton-
review based on four randomized controlled trials resulted in sensing proteins which prevent the actin polymerization (F-actin)/
short-term improvements in metabolic syndrome components depolymerization (G-actin) process, which impedes cellular func-
following paleo diet [34]. A 4-month consumption of a paleo diet tions [64,65]. Together, they affect vesicular trafficking, autophagy,
improved glucose control and lipid profiles in people with type 2 innate immunity, angiogenesis, proliferation, metastasis, apoptosis,
diabetes, compared with conventional diet (comprising moderate etc. [58,66e68]. Drug resistanceemediating efflux protein, the P-
salt intake, low-fat dairy, whole grains, and legumes) [35]. Con- glycoprotein, activity is increased by low intracellular calcium
sumption of paleo diet increased incretin and anorectic gut hor- levels and high acidic pH [69e72]. Cancer-associated receptor
mones (glucagon-like peptide-1 and peptide YY), which improved proteins, the G proteinecoupled receptors such as ovarian cancer G
satiety[36]. Paleo diet is rich in Kþ. Deficiency of this ion has been protein-coupled receptor 1, G protein-coupled receptor 4, and T-cell
implicated in cardiovascular diseases, kidney stones, and osteopo- death-associated gene 8 act as proton sensors [73,74]. Subsequently,
rosis. Therefore, a Kþ-rich paleo diet might have enough of this ion channels such as the proton-gated sodium channels are
mineral to prevent the need of drugs or supplements [37]. A manipulated, and this ionic perturbation leads to pain [75e77].
comparative study between the Western diet and paleo diet reveals Paleo diets are dominated by plant products and are not pro-
that the latter can inhibit mammalian target of rapamycin complex cessed. Therefore, the polyphenolic phytochemicals quench reac-
1 signaling, thus exerting effect on cell growth, proliferation, and tive oxygen species and lower acidity [47,78e80]. Fig. 2 illustrates
angiogenesis [38]. In a case study, a female in her sixth decade, the mechanism of the Western diet and paleo diet mediating
when subsisted on paleo-pattern food, her glycemic load and blood pathogenesis and restoring homeostasis, respectively.
pressure issues were resolved [39].
Discussion
Western diet
Owing to the inappropriate diet, by the time the individuals
The Western diet is the reverse of paleo diet, which is dominated reach their forties, inflammatory diseases affect them. To get rid of
by high glucose, dairy protein, saturated fats, and trans fats [40,41]. the pathology, people seek sugar-free, fat-free, gluten-free, and
Furthermore, this diet is brimming with sugar, salt, lipid, and ad- probiotics-enriched diets. Awareness and moderation in food
ditives. Preservatives like sulfites, nitrites, benzoic acid, emulsifier habits can go a long way in health retention. Inflammatory food
agents (polysorbate-80), and colors are being added liberally to the consumption should be minimized to achieve optimal physiological
food for the augmentation of shelf-life and esthetic appeal. Such diet pH of the body [81]. The inclusion of alkalogenic foods such as
includes cheese, pizza, pasta, french fries, chocolates, mayonnaise, citrate, etc. in diet should be increased [42]. In fact, the Mediter-
soft drinks, processed meat, and frozen foods [42,43]. Dairy ranean food comprising whole grains, fruits, nuts, vegetable, seeds,
S. Patel, H.A.R. Suleria / Paleolithic diet to prevent inflammation and acidosis 239

D, which is needed for health [5,92]. Also, the hunteregatherer era


Glycemic control involved raw consumption of food or probably limited fire usage.
Fruits
Normalize blood pressure Therefore, the food is likely to contain gliadin, lectins, and saponins.
Vegetables Modulate lipid profile These components are known to evoke immune response and to
Decline in weight
Tubers cause intestinal porosity [5,93,94]. A study hypothesizes that
Nuts Decline C-reactive protein
Drop in glycated haemoglobin (HbAlc) cooked foods required less energy for digestion, which led to the
Lean meat
enhancement in brain size [95]. It challenges the benefit claims of
paleo diet. These hypotheses are worthy of testing.
Paleo diet Also, modern diet with high protein may be harmful for adults,
Type II diabetes
Acne but not for adolescents. Furthermore, thousand years of evolution
Metabolic
acidosis Tumor has generated diverse genotypes. Therefore, a “one-size-fits-all”
Oxidative stress Sepsis dietary pattern is not going to help. Therefore, adherence to
Inflammation Crohn’s disease
Obesity
personalized diet is important [96]. Apart from that, depending on
High glucose Non-alcoholic fatty liver disease age, health status, and co-morbidity, the food habits need to be
Dairy protein Cardiovascular disease revised. In an inflammatory condition, an individual who used to
Saturated fats Chronic kidney disease
Trans fats digest animal proteinebased foods might develop skin rashes
Faster bone resorption
Western diet Additives Brain ischemia
while someone who used to metabolize dairy products might show
intolerance.
Finally, it is important to realize that apart from diet, other
factors are causal of inflammation. These nondiet factors include
infections (virus, bacteria, protozoa, nematode, and fungi), aller-
Fig. 2. The mechanism of the Western diet and paleo diet mediating pathogenesis and
restoring homeostasis, respectively. Western diet causes oxidative stress and inflam- gens (plant pollen, arthropod chitins, metal, etc.), and occupational
mation. It leads to metabolic acidosis and other pathologies. Paleo diet, dominated by exposures [97e99]. The all-pervasive pollution, reckless usage of
fruits and vegetables, ameliorates blood parameters. drugs, and chemical toiletries are other cardinal inflammatory
agents [100e103]. Therefore, before attributing paleo diets as
legumes, potatoes, and herbs is regarded the healthiest because of antiinflammatory, effects of these agents ought to be verified. If an
its alkalogenic ingredients [82e85]. individual's lifestyle includes above inflammatory agents, the best
Paleo diet is much ancient than diverse repertoire of ethnic di- of nutritious diet, be that paleo or ethnic origin, cannot help alle-
ets. Thousand years of evolution, geographical relocations, and viate a health condition. For systemic well-being, a holistic and
cultural practices led to the emergence of ethnic diet, from the disciplined life is of paramount importance.
paleo diet. Ethnic diets vary in their nutritional values, while some
of them might be better than modern diet, some may not be. Biryani Conclusion
and burrito are heavy in spice and oils, whereas injera is made of
humble ingredients; poke and sushi are minimally processed. Acidogenic foods lead to drop in body pH, which initiate a
Furthermore, the ingredients used in the preparation of these cascade of enzyme activation, inflammation, and tumors. In this
ethnic foods need consideration while determining the food safety. regard, dietary correction by adoption of paleo diet appears to be a
Raw foods like might contain Norovirus [86], while the health ef- holistic solution toward good health. Several clinical cases and
fects of soy, sesame, etc., are debatable due to the role of phy- cohort studies have proven that paleo diet is capable of preventing
toestrogens (isoflavone and lignan) present in them [87e89]. metabolic syndrome, but the consumers' age, gender, and health
The current generation is focused mostly on weight loss and status are critical parameters in its efficacy.
muscle development. Therefore, they do not hesitate to take ste-
roids or supplements. These ingredients might be showing instant
Conflicts of interest
effect but in a long run they are not beneficial for the body. Whey
protein [90], branched-chain amino acids (leucine, isoleucine, and
The authors have no conflicts of interest to declare.
valine), carnosine, L-arginine, glutamine, carnitine, ZMA (blend of
zinc, magnesium aspartate, and vitamin B6), high molecular-
weight carbohydrates, and beta-ecdysterone are nourishing for Compliance with ethical standards
the musculoskeletal system, but these components are also neu-
rotransmitters; therefore, they lead to other health problems. This work does not involve human participants or animal
Questions arise if paleo diet can meet the nutritional require- models.
ment of humans? Plant-based foods are low in calcium and vitamin
D, the components essential for skeletal system health [1]. In that References
case, modern dietary ingredients should be used in moderation.
[1] Klonoff DC. The beneficial effects of a Paleolithic diet on type 2 diabetes and
However, it is important to understand the links. In diseases like other risk factors for cardiovascular disease. J Diabetes Sci Technol 2009;3:
osteoporosis, calcium is lost by bone demineralization. That does 1229e32.
not mean one should take high doses of calcium supplements, as it €nsson T, Granfeldt Y, Ahre
[2] Jo n B, Branell U-C, Pålsson G, Hansson A,
€ derstro
So €m M and Lindeberg S. Beneficial effects of a Paleolithic diet on
will put strain on the kidneys [91]. Calcium is lost from bone, when cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot
the body fluid becomes acidic. It can be hypothesized that as paleo study. Cardiovasc Diabetol 2009;8:35. https://doi.org/10.1186/1475-2840-8-
diet is not likely to raise acidity, calcium loss should not be an issue. 35.
[3] Tarantino G, Citro V and Finelli C. Hype or reality: should patients with
Another publication also supports this hypothesis reporting that
metabolic syndrome-related NAFLD be on the hunter-gatherer (paleo) diet to
paleo diet has low phytates and sodium chloride content; therefore, decrease morbidity? J Gastrointest Liver Dis 2015;24:359e68.
it is less likely to increase acidosis [5]. [4] Liu L, Bestel S, Shi J, Song Y and Chen X. Paleolithic human exploitation of
The arguments that can be made against the inefficacy of paleo plant foods during the last glacial maximum in North China. Proc Natl Acad
Sci U S A 2013;110:5380e5. https://doi.org/10.1073/pnas.1217864110.
food have been outlined below. Dairy products like cheese and [5] Kowalski LM and Bujko J. Evaluation of biological and clinical potential of
butter are acidogenic and insulinotropic, but they provide vitamin paleolithic diet. Rocz Panstw Zakl Hig 2012;63:9e15.
240 J Ethn Foods 2017; 4: 236e241

[6] Demigne  C, Sabboh H, Re mesy C and Meneton P. Protective effects of high hunter-gatherer type diet. Eur J Clin Nutr 2009;63:947e55. https://doi.org/
dietary potassium: nutritional and metabolic aspects. J Nutr 2004;134: 10.1038/ejcn.2009.4.
2903e6. [32] Otten J, Stomby A, Waling M, Isaksson A, Tellstro €m A, Lundin-Olsson L,
[7] Singh RK, Wheildon N and Ishikawa S. Food additive P-80 impacts mouse gut Brage S, Ryberg M, Svensson M and Olsson T. Benefits of a Paleolithic diet
microbiota promoting intestinal inflammation. Obes Liver Dysfunct SOJ with and without supervised exercise on fat mass, insulin sensitivity, and
Microbiol Infect Dis 2016:4. glycemic control: a randomized controlled trial in individuals with type 2
[8] Rockwell S, Dobrucki IT, Kim EY, Marrison ST and Vu VT. Hypoxia and ra- diabetes. Diabetes Metab Res Rev 2016. https://doi.org/10.1002/dmrr.2828.
diation therapy: past history, ongoing research, and future promise. Curr Mol [33] Boers I, Muskiet FA, Berkelaar E, Schut E, Penders R, Hoenderdos K,
Med 2009;9:442e58. Wichers HJ and Jong MC. Favourable effects of consuming a Palaeolithic-type
[9] Peng X and Gandhi V. ROS-activated anticancer prodrugs: a new strategy for diet on characteristics of the metabolic syndrome: a randomized controlled
tumor-specific damage. Ther Deliv 2012;3:823e33. pilot-study. Lipids Health Dis 2014;13:160. https://doi.org/10.1186/1476-
[10] McKeown SR. Defining normoxia, physoxia and hypoxia in tumours- 511X-13-160.
implications for treatment response. Br J Radiol 2014;87:20130676. [34] Manheimer EW, van Zuuren EJ, Fedorowicz Z and Pijl H. Paleolithic nutrition
https://doi.org/10.1259/bjr.20130676. for metabolic syndrome: systematic review and meta-analysis. Am J Clin
[11] Kuipers RS, Joordens JCA and Muskiet FAJ. A multidisciplinary reconstruction Nutr 2015;102:922e32. https://doi.org/10.3945/ajcn.115.113613.
of Palaeolithic nutrition that holds promise for the prevention and treatment [35] Masharani U, Sherchan P, Schloetter M, Stratford S, Xiao A, Sebastian A, Nolte
of diseases of civilisation. Nutr Res Rev 2012;25:96e129. https://doi.org/ Kennedy M and Frassetto L. Metabolic and physiologic effects from
10.1017/S0954422412000017. consuming a hunter-gatherer (Paleolithic)-type diet in type 2 diabetes. Eur J
[12] Booth FW, Chakravarthy MV and Spangenburg EE. Exercise and gene Clin Nutr 2015;69:944e8. https://doi.org/10.1038/ejcn.2015.39.
expression: physiological regulation of the human genome through physical [36] Bligh HFJ, Godsland IF, Frost G, Hunter KJ, Murray P, MacAulay K, Hyliands D,
activity. J Physiol 2002;543:399e411. https://doi.org/10.1113/jphysiol. Talbot DC, Casey J, Mulder TP and Berry MJ. Plant-rich mixed meals based on
2002.019265. Palaeolithic diet principles have a dramatic impact on incretin, peptide YY
[13] Broussard-Marin L and Hynak-Hankinson MT. Ethnic food: the use of Cajun and satiety response, but show little effect on glucose and insulin homeo-
cuisine as a model. J Am Diet Assoc 1989;89:1117e21. stasis: an acute-effects randomised study. Br J Nutr 2015;113:574e84.
[14] Abu-Saad K, Shahar DR, Vardi H and Fraser D. Importance of ethnic foods as https://doi.org/10.1017/S0007114514004012.
predictors of and contributors to nutrient intake levels in a minority popu- [37] Palmer BF and Clegg DJ. Achieving the benefits of a high-potassium, paleo-
lation. Eur J Clin Nutr 2010;64:S88e94. https://doi.org/10.1038/ejcn. lithic diet, without the toxicity. Mayo Clin Proc 2016;91:496e508. https://
2010.217. doi.org/10.1016/j.mayocp.2016.01.012.
[15] Burrowes JD. Incorporating ethnic and cultural food preferences in the renal [38] Melnik BC. Linking diet to acne metabolomics, inflammation, and comedo-
diet. Adv Ren Replace Ther 2004;11:97e104. genesis: an update. Clin Cosmet Investig Dermatol 2015;8:371e88. https://
[16] Khokhar S, Marletta L, Shahar DR, Farre R, Ireland JD, Jansen-van der Vliet M, doi.org/10.2147/CCID.S69135.
De Henauw S and Finglas P, Participants of EuroFIR Ethnic Foods Work Pack- [39] Coetzee O and Filatova D. Metabolic syndrome reversal through nutrition: a
age. New food composition data on selected ethnic foods consumed in Europe. case report. 2016. https://doi.org/10.1016/j.aimed.2016.07.007.
Eur J Clin Nutr 2010;64:S82e7. https://doi.org/10.1038/ejcn.2010.216. [40] Hu FB. Are refined carbohydrates worse than saturated fat? Am J Clin Nutr
[17] Gleadow R, Pegg A and Blomstedt CK. Resilience of cassava (Manihot escu- 2010;91:1541e2. https://doi.org/10.3945/ajcn.2010.29622.
lenta Crantz) to salinity: implications for food security in low-lying regions. [41] Myles IA. Fast food fever: reviewing the impacts of the Western diet on
J Exp Bot 2016;67:5403e13. https://doi.org/10.1093/jxb/erw302. immunity. Nutr J 2014;13:61. https://doi.org/10.1186/1475-2891-1C3-61.
[18] Khandare AL, Babu JJ, Ankulu M, Aparna N, Shirfule A and Rao GS. Grass pea [42] Jehle S, Zanetti A, Muser J, Hulter HN and Krapf R. Partial neutralization of
consumption & present scenario of neurolathyrism in Maharashtra State of the acidogenic Western diet with potassium citrate increases bone mass in
India. Indian J Med Res 2014;140:96e101. postmenopausal women with osteopenia. J Am Soc Nephrol 2006;17:
[19] Singh SS and Rao SLN. Lessons from neurolathyrism: a disease of the past & 3213e22. https://doi.org/10.1681/ASN.2006030233.
the future of Lathyrus sativus (Khesari dal). Indian J Med Res 2013;138:32e7. [43] Schwalfenberg GK. The alkaline diet: is there evidence that an alkaline pH
[20] Bradley WG and Mash DC. Beyond Guam: the cyanobacteria/BMAA hy- diet benefits health? J Environ Public Health 2012;2012:727630. https://
pothesis of the cause of ALS and other neurodegenerative diseases. Amyo- doi.org/10.1155/2012/727630.
troph Lateral Scler 2009;10(Suppl. 2):7e20. https://doi.org/10.3109/ [44] Malekinejad H and Rezabakhsh A. Hormones in dairy foods and their impact
17482960903286009. on public health e a narrative review article. Iran J Public Health 2015;44:
[21] Anraku K, Nonaka K, Yamaga T, Yamamoto T, Shin M-C, Wakita M, 742e58.
Hamamoto A and Akaike N. Removal of toxin (tetrodotoxin) from puffer [45] Stephany RW. Hormonal growth promoting agents in food producing ani-
ovary by traditional fermentation. Toxins (Basel) 2013;5:193e202. https:// mals. Handb Exp Pharmacol 2010:355e67. https://doi.org/10.1007/978-3-
doi.org/10.3390/toxins5010193. 540-79088-4_16.
[22] Patel S. Nutrition, safety, market status quo appraisal of emerging functional [46] Miller KD and Milne P. Determination of low-level pesticide residues in soft
food corn smut (huitlacoche). Trends Food Sci Technol 2016;57:93e102. drinks and sports drinks by liquid chromatography with tandem mass
https://doi.org/10.1016/j.tifs.2016.09.006. spectrometry: collaborative study. J AOAC Int 2008;91:181e201.
[23] Handley MA, Hall C, Sanford E, Diaz E, Gonzalez-Mendez E, Drace K, [47] Scialla JJ and Anderson CAM. Dietary acid load: a novel nutritional target in
Villalobos M and Croughan M. Globalization, binational communities, and chronic kidney disease? Adv Chronic Kidney Dis 2013;20:141e9. https://
imported food risks: results of an outbreak investigation of lead poisoning in doi.org/10.1053/j.ackd.2012.11.001.
Monterey County, California. Am J Public Health 2007;97:900e6. https:// [48] Maurer M, Riesen W, Muser J, Hulter HN and Krapf R. Neutralization of
doi.org/10.2105/AJPH.2005.074138. Western diet inhibits bone resorption independently of K intake and reduces
[24] Cesard N, Komatsu S and Iwata A. Processing insect abundance: trading and cortisol secretion in humans. Am J Physiol Ren Physiol 2003;284:F32e40.
fishing of zazamushi in Central Japan (Nagano Prefecture, Honshu  Island). https://doi.org/10.1152/ajprenal.00212.2002.
J Ethnobiol Ethnomed 2015;11:78. https://doi.org/10.1186/s13002-015- [49] Cao S, Liu P, Zhu H, Gong H, Yao J, Sun Y, Geng G, Wang T, Feng S, Han M,
0066-7. Zhou J and Xu Y. Extracellular acidification acts as a key modulator of
[25] Manca G, Porcu A, Ru A, Salaris M, Franco MA and De Santis EPL. Comparison neutrophil apoptosis and functions. PLoS One 2015;10:e0137221. https://
of g-aminobutyric acid and biogenic amine content of different types of doi.org/10.1371/journal.pone.0137221.
ewe's milk cheese produced in Sardinia, Italy. Ital J Food Saf 2015;4:4700. [50] Papamichael K, Konstantopoulos P and Mantzaris GJ. Helicobacter pylori
https://doi.org/10.4081/ijfs.2015.4700. infection and inflammatory bowel disease: is there a link? World J Gastro-
[26] Jia X, Lee HF, Cui M, Liu C, Zeng L, Yue RPH, Zhao Y and Lu H. Habitat vari- enterol 2014;20:6374e85. https://doi.org/10.3748/wjg.v20.i21.6374.
ability and ethnic diversity in Northern Tibetan Plateau. Sci Rep 2017;7:918. [51] Rajam€ € m T, Nurmi K, Åkerman KEO, Kovanen PT, O
aki K, Nordstro €o
€rni K and
https://doi.org/10.1038/s41598-017-01008-8. Eklund KK. Extracellular acidosis is a novel danger signal alerting innate
[27] Lawson DW, Borgerhoff Mulder M, Ghiselli ME, Ngadaya E, Ngowi B, immunity via the NLRP3 inflammasome. J Biol Chem 2013;288:13410e9.
Mfinanga SGM, Hartwig K and James S. Ethnicity and child health in https://doi.org/10.1074/jbc.M112.426254.
northern Tanzania: Maasai pastoralists are disadvantaged compared to [52] Wang X-J, Cao Q, Zhang Y and Su X-D. Activation and regulation of
neighbouring ethnic groups. PLoS One 2014;9:e110447. https://doi.org/ caspase-6 and its role in neurodegenerative diseases. Annu Rev Pharmacol
10.1371/journal.pone.0110447. Toxicol 2015;55:553e72. https://doi.org/10.1146/annurev-pharmtox-010
[28] Moon JM and Chun BJ. Severe coagulopathy after ingestion of “Snake Wine”. 814-124414.
J Emerg Med 2016;50:848e51. https://doi.org/10.1016/j.jemermed.2015. [53] Wong AKF, Howie J, Petrie JR and Lang CC. AMP-activated protein kinase
11.037. pathway: a potential therapeutic target in cardiometabolic disease. Clin Sci
[29] Patel S and Meher BR. A review on emerging frontiers of house dust mite and (Lond) 2009;116:607e20. https://doi.org/10.1042/CS20080066.
cockroach allergy research. Allergol Immunopathol (Madr) 2016. https:// [54] Page-McCaw A, Ewald AJ and Werb Z. Matrix metalloproteinases and the
doi.org/10.1016/j.aller.2015.11.001. regulation of tissue remodelling. Nat Rev Mol Cell Biol 2007;8:221e33.
[30] Patel S, Hazel CM, Winterton AGM and Mortby E. Survey of ethnic foods for https://doi.org/10.1038/nrm2125.
mycotoxins. Food Addit Contam 1996;13:833e41. https://doi.org/10.1080/ [55] Konieczna I, Zarnowiec P, Kwinkowski M, Kolesinska B, Fraczyk J, Kaminski Z
02652039609374470. and Kaca W. Bacterial urease and its role in long-lasting human diseases.
[31] Frassetto LA, Schloetter M, Mietus-Synder M, Morris RC and Sebastian A. Curr Protein Pept Sci 2012;13:789e806. https://doi.org/10.2174/1389203
Metabolic and physiologic improvements from consuming a paleolithic, 12804871094.
S. Patel, H.A.R. Suleria / Paleolithic diet to prevent inflammation and acidosis 241

[56] Levine B and Kroemer G. Autophagy in the pathogenesis of disease. Cell Med Sci Sports Exerc 2010;42:1279e85. https://doi.org/10.1249/MSS.0b0
2008;132:27e42. https://doi.org/10.1016/j.cell.2007.12.018. 13e3181ce61a5.
[57] Vannini F, Kashfi K and Nath N. The dual role of iNOS in cancer. Redox Biol [79] Grabacka MM, Gawin M and Pierzchalska M. Phytochemical modulators of
2015;6:334e43. https://doi.org/10.1016/j.redox.2015.08.009. mitochondria: the search for chemopreventive agents and supportive ther-
[58] Pan J, Sun L-C, Tao Y-F, Zhou Z, Du X-L, Peng L, Feng X, Wang J, Li Y-P, Liu L, apeutics. Pharmaceuticals (Basel) 2014;7:913e42. https://doi.org/10.3390/
Wu S-Y, Zhang Y-L, Hu S-Y, Zhao W-L, Zhu X-M, Lou G-L and Ni J. ATP ph7090913.
synthase ecto-a-subunit: a novel therapeutic target for breast cancer. J Transl [80] Kumar GP and Khanum F. Neuroprotective potential of phytochemicals.
Med 2011;9:211. https://doi.org/10.1186/1479-5876-9-211. Pharmacogn Rev 2012;6:81e90. https://doi.org/10.4103/0973-7847.99898.
[59] Zucker S, Schmidt CE, Dufour A, Kaplan RC, Park HI and Jiang W. ProMMP-2: [81] Robey IF. Examining the relationship between diet-induced acidosis and cancer.
TIMP-1 complexes identified in plasma of healthy individuals. Connect Tis- Nutr Metab (Lond) 2012;9:72. https://doi.org/10.1186/1743-7075-9-72.
sue Res 2009;50:223e31. https://doi.org/10.1080/03008200802626970. [82] Altomare R, Cacciabaudo F, Damiano G, Palumbo VD, Gioviale MC, Bellavia M,
[60] Vartak DG and Gemeinhart RA. Matrix metalloproteases: underutilized tar- Tomasello G and Lo Monte AI. The mediterranean diet: a history of health.
gets for drug delivery. J Drug Target 2007;15:1e20. https://doi.org/10.1080/ Iran J Public Health 2013;42:449e57.
10611860600968967. [83] Del Chierico F, Vernocchi P, Dallapiccola B and Putignani L. Mediterranean
[61] Ricciotti E and FitzGerald GA. Prostaglandins and inflammation. Arterioscler diet and health: food effects on gut microbiota and disease control. Int J Mol
Thromb Vasc Biol 2011;31:986e1000. https://doi.org/10.1161/ATVBAHA. Sci 2014;15:11678e99. https://doi.org/10.3390/ijms150711678.
110.207449. [84] Dontas AS, Zerefos NS, Panagiotakos DB, Vlachou C and Valis DA. Mediter-
[62] Demura M, Martin RM, Shozu M, Sebastian S, Takayama K, Hsu W-T, ranean diet and prevention of coronary heart disease in the elderly. Clin
Schultz RA, Neely K, Bryant M, Mendonca BB, Hanaki K, Kanzaki S, Interv Aging 2007;2:109e15.
Rhoads DB, Misra M and Bulun SE. Regional rearrangements in chromosome [85] Castro-Quezada I, Roma n-Vin
~ as B and Serra-Majem L. The Mediterranean
15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene. diet and nutritional adequacy: a review. Nutrients 2014;6:231e48. https://
Hum Mol Genet 2007;16:2529e41. https://doi.org/10.1093/hmg/ddm145. doi.org/10.3390/nu6010231.
[63] Riemann A, Schneider B, Ihling A, Nowak M, Sauvant C, Thews O and [86] Maunula L, Ro €nnqvist M, Åberg R, Lunden J and Nevas M. The presence of
Gekle M. Acidic environment leads to ROS-induced MAPK signaling in cancer norovirus and adenovirus on environmental surfaces in relation to the hy-
cells. PLoS One 2011;6:e22445. https://doi.org/10.1371/ gienic level in food service operations associated with a suspected gastro-
journal.pone.0022445. enteritis outbreak. Food Environ Virol 2017;9:334. https://doi.org/10.1007/
[64] Damaghi M, Wojtkowiak JW and Gillies RJ. pH sensing and regulation in s12560-017-9291-7.
cancer. Front Physiol 2013;4:370. https://doi.org/10.3389/fphys.2013.00370. [87] Nehybova 
 T, Smarda J and Benes P. Plant coumestans: recent advances and
[65] Dominguez R and Holmes KC. Actin structure and function. Annu Rev Biophys future perspectives in cancer therapy. Anticancer Agents Med Chem
2011;40:169e86. https://doi.org/10.1146/annurev-biophys-042910-155359. 2014;14:1351e62.
[66] Henkels KM, Boivin GP, Dudley ES, Berberich SJ and Gomez-Cambronero J. [88] Vitale DC, Piazza C, Melilli B, Drago F and Salomone S. Isoflavones: estrogenic
Phospholipase D (PLD) drives cell invasion, tumor growth and metastasis in a activity, biological effect and bioavailability. Eur J Drug Metab Pharmacokinet
human breast cancer xenograph model. Oncogene 2013;32:5551e62. 2013;38:15e25. https://doi.org/10.1007/s13318-012-0112-y.
https://doi.org/10.1038/onc.2013.207. [89] Adlercreutz H. Lignans and human health. Crit Rev Clin Lab Sci 2007;44:
[67] Bruntz RC, Lindsley CW and Brown HA. Phospholipase D signaling pathways 483e525. https://doi.org/10.1080/10408360701612942.
and phosphatidic acid as therapeutic targets in cancer. Pharmacol Rev [90] Patel S. Emerging trends in nutraceutical applications of whey protein and its
2014;66:1033e79. https://doi.org/10.1124/pr.114.009217. derivatives. J Food Sci Technol 2015;52:6847e58. https://doi.org/10.1007/
[68] Koliopanos A, Friess H, Kleeff J, Shi X, Liao Q, Pecker I, Vlodavsky I, s13197-015-1894-0.
Zimmermann A and Büchler MW. Heparanase expression in primary and [91] Sorensen MD. Calcium intake and urinary stone disease. Transl Androl Urol
metastatic pancreatic cancer. Cancer Res 2001;61:4655e9. 2014;3:235e40. https://doi.org/10.3978/j.issn.2223-4683.2014.06.05.
[69] Germann UA, Pastan I and Gottesman MM. P-glycoproteins: mediators of [92] Schmid A and Walther B. Natural vitamin D content in animal products. Adv
multidrug resistance. Semin Cell Biol 1993;4:63e76. https://doi.org/10.1006/ Nutr 2013;4:453e62. https://doi.org/10.3945/an.113.003780.
scel.1993.1008. [93] Podolak I, Galanty A and Sobolewska D. Saponins as cytotoxic agents: a re-
[70] Damiani D, Tiribelli M, Calistri E, Geromin A, Chiarvesio A, Michelutti A, view. Phytochem Rev 2010;9:425e74. https://doi.org/10.1007/s11101-010-
Cavallin M and Fanin R. The prognostic value of P-glycoprotein (ABCB) and 9183-z.
breast cancer resistance protein (ABCG2) in adults with de novo acute [94] Matsushita M. Ficolins: complement-activating lectins involved in innate
myeloid leukemia with normal karyotype. Haematologica 2006;91:825e8. immunity. J Innate Immun 2010;2:24e32. https://doi.org/10.1159/
[71] Leonard GD, Fojo T and Bates SE. The role of ABC transporters in clinical 000228160.
practice. Oncologist 2003;8:411e24. [95] Roebroeks W and Villa P. On the earliest evidence for habitual use of fire in
[72] Wojtkowiak JW, Verduzco D, Schramm KJ and Gillies RJ. Drug resistance and Europe. Proc Natl Acad Sci U S A 2011;108:5209e14. https://doi.org/
cellular adaptation to tumor acidic pH microenvironment. Mol Pharm 10.1073/pnas.1018116108.
2011;8:2032e8. https://doi.org/10.1021/mp200292c. [96] Tollefsbol TO, Lindroth AM, Park JH, Yoo Y and Park YJ. Chapter 11 e
[73] de Vallie re C, Wang Y, Eloranta JJ, Vidal S, Clay I, Spalinger MR, nutriepigenomics: personalized nutrition meets epigenetics. Pers Epigenet
Tcymbarevich I, Terhalle A, Ludwig MG, Suply T, Fried M, Kullak-Ublick GA, 2015:313e47. https://doi.org/10.1016/B978-0-12-420135-4.00011-5.
Frey-Wagner I, Scharl M, Seuwen K, Wagner CA and Rogler G. G protein- [97] Smole U, Wagner S, Balazs N, Radauer C, Bublin M, Allmaier G, Hoffmann-
coupled pH-sensing receptor OGR1 is a regulator of intestinal inflammation. Sommergruber K and Breiteneder H. Bet v 1 and its homologous food
Inflamm Bowel Dis 2015;21:1269e81. https://doi.org/10.1097/ allergen Api g 1 stimulate dendritic cells from birch pollen-allergic in-
MIB.0000000000000375. dividuals to induce different Th-cell polarization. Allergy 2010;65:1388e96.
[74] Ihara Y, Kihara Y, Hamano F, Yanagida K, Morishita Y, Kunita A, Yamori T, https://doi.org/10.1111/j.1398-9995.2010.02407.x.
Fukayama M, Aburatani H, Shimizu T and Ishii S. The G protein-coupled [98] Do DC, Zhao Y and Gao P. Cockroach allergen exposure and risk of asthma.
receptor T-cell death-associated gene 8 (TDAG8) facilitates tumor develop- Allergy 2016;71:463e74. https://doi.org/10.1111/all.12827.
ment by serving as an extracellular pH sensor. Proc Natl Acad Sci U S A [99] Walker MD and Zunt JR. Neuroparasitic infections: cestodes, trematodes, and
2010;107:17309e14. https://doi.org/10.1073/pnas.1001 protozoans. Semin Neurol 2005;25:262e77. https://doi.org/10.1055/s-2005-
165107. 917663.
[75] Li M-H, Leng T-D, Feng X-C, Yang T, Simon RP and Xiong Z-G. Modulation of [100] Evans GS, Cadogan D, Flueckiger A, Hennes C and Kimber I. Chemical
acid-sensing ion channel 1a by intracellular pH and its role in ischemic pollution, respiratory allergy and asthma: a perspective. J Appl Toxicol
stroke. J Biol Chem 2016;291:18370e83. https://doi.org/10.1074/jbc.M115. 2008;28:1e5. https://doi.org/10.1002/jat.1294.
713636. [101] Cohen AJ. Outdoor air pollution and lung cancer. Environ Health Perspect
[76] Li W-G and Xu T-L. Acid-sensing ion channels: a novel therapeutic target for 2000;108(Suppl.):743e50.
pain and anxiety. Curr Pharm Des 2015;21:885e94. [102] Yew WW and Leung CC. Antituberculosis drugs and hepatotoxicity. Respir-
[77] Wemmie JA, Taugher RJ and Kreple CJ. Acid-sensing ion channels in pain and ology 2006;11:699e707. https://doi.org/10.1111/j.1440-1843.2006.00941.x.
disease. Nat Rev Neurosci 2013;14:461e71. https://doi.org/10.1038/nrn3529. [103] Bagasra O, Golkar Z, Garcia M, Rice LN and Pace DG. Role of perfumes in
[78] Kon M, Ikeda T, Homma T, Akimoto T, Suzuki Y and Kawahara T. Effects of pathogenesis of autism. Med Hypotheses 2013;80:795e803. https://doi.org/
acute hypoxia on metabolic and hormonal responses to resistance exercise. 10.1016/j.mehy.2013.03.014.

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