https://www.science.org/doi/10.1126/science.adn5421

The Role of the FADS Gene and Inflammatory Cascade in African Americans

1. FADS Gene Variants and Elevated Arachidonic Acid (AA)

Approximately 80% of African Americans carry a variant in the FADS gene (rs174537), significantly higher than the ~40% prevalence among European Americans. This variant enhances the efficiency of converting dietary linoleic acid (LA), an omega-6 fatty acid commonly found in processed foods, into arachidonic acid (AA) (Sergeant et al., 2012; Blasbalg et al., 2011; Chilton et al., 2022). Due to the prevalent Western diet rich in omega-6, African Americans with this FADS variant tend to have higher average serum AA levels (0.20-0.24 mg/dL) compared to White Americans (0.15-0.18 mg/dL) (Sergeant et al., 2012; Blasbalg et al., 2011). High AA levels contribute to an inflammatory profile, with research indicating that 50-75% of African Americans exceed the AA healthy threshold of 0.20-0.25 mg/dL, while only 10-20% of White Americans exceed this limit (Sergeant et al., 2012).

2. Inflammatory Cascade and Elevated IL-6 and CRP

High AA levels activate pathways that produce pro-inflammatory cytokines, contributing to chronic inflammation. Two key markers—interleukin-6 (IL-6) and C-reactive protein (CRP)—are commonly elevated in African Americans. Average IL-6 levels for African Americans are around 2.5-3.5 pg/mL, about 25-40% higher than the 1.8-2.5 pg/mL observed in White Americans (Palermo et al., 2024). IL-6 levels above the healthy threshold (3.0-5.0 pg/mL) are observed in 30-50% of African Americans, compared to only 10-20% of White Americans (Palermo et al., 2024). This cytokine plays a role in immune response regulation and is associated with higher risks of metabolic syndrome and cardiovascular disease, both of which disproportionately affect African Americans (Cushman et al., 2024; Jackson Heart Study, 2021).

CRP levels also reflect this inflammatory pattern. African Americans average between 3.0-5.5 mg/L in CRP, which is 40-60% higher than the levels observed in White Americans (2.0-3.5 mg/L). Elevated CRP, generally associated with heightened cardiovascular disease risk, affects 40-60% of African Americans beyond the healthy threshold of 3.0 mg/L, while only 20-30% of White Americans exceed this level (Cushman et al., 2024; Palermo et al., 2024).

3. Potential Impact of an Omega-Balanced Food Environment

While increasing omega-3 intake is beneficial for reducing inflammation, it is not sufficient on its own. Both omega-3 and omega-6 fatty acids play distinct roles in inflammation: omega-3s are generally anti-inflammatory, whereas omega-6s are typically pro-inflammatory (Simopoulos, 2002; Chilton et al., 2022). These fatty acids compete for the same receptors and enzymatic pathways in the body (Calder, 2006; Chilton et al., 2022), so maintaining an appropriate balance between them is essential. Notably, simply increasing omega-3 intake may not effectively counterbalance high omega-6 levels, as fatty acid receptors can reach saturation and thus will not absorb more omega-3s beyond a certain point (Calder, 2006; Simopoulos, 2008). Therefore, reducing omega-6 intake, alongside maintaining adequate omega-3 levels, is critical for controlling inflammation.

In cases where certain FADS gene variants are present, limiting omega-6 intake may be necessary to avoid inflammation that arises from excessive AA production (Chilton et al., 2022). This targeted approach to managing omega intake aligns with the need for an omega-balanced food environment, particularly to mitigate health risks within African American communities who are disproportionately affected by high AA levels.

In conclusion, equitable access to a balanced diet, less reliant on omega-6-rich processed foods, could benefit African American communities substantially, reducing the prevalence of chronic inflammation and its associated health and economic burdens.

References

1.	Sergeant, S., Hugenschmidt, C. E., Rudock, M. E., et al. “Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans.” British Journal of Nutrition, 107(4), 547-555, 2012.
2.	Blasbalg, T. L., Hibbeln, J. R., Ramsden, C. E., et al. “Changes in consumption of omega-3 and omega-6 fatty acids in the United States.” American Journal of Clinical Nutrition, 93(5), 950-962, 2011.
3.	Simopoulos, A. P. “The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases.” Experimental Biology and Medicine, 227(5), 365-367, 2002.
4.	Calder, P. C. “Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale.” Biochimie, 88(1), 201-212, 2006.
5.	Palermo, B. J., Wilkinson, K. S., Plante, T. B., et al. “Interleukin-6, diabetes, and metabolic syndrome in a biracial cohort: REGARDS study.” Diabetes Care, 47(3), 491-500, 2024.
6.	Cushman, M., Long, D. L., Olson, N. C., et al. “Racial differences in inflammatory markers and cardiovascular disease risk.” Nephrology Dialysis Transplantation, 36(3), 561-570, 2024.
7.	Chilton, F. H., Manichaikul, A., Yang, C., et al. “Interpreting Clinical Trials With Omega-3 Supplements in the Context of Ancestry and FADS Genetic Variation.” Frontiers in Nutrition, PMCID: PMC8861490, 2022.
8.	Jackson Heart Study. “Health disparities in cardiovascular disease in African Americans.” Diabetes Care, 2021.

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Abstract: A high-quality diet during pregnancy may have positive effects on fetal growth and nutritional status at birth, and it may modify the risk of developing chronic diseases later in life. The aim of this study was to evaluate the association between diet quality and newborn nutritional status in a group of pregnant Mexican women. As part of the ongoing Mexican prospective cohort study, OBESO, we studied 226 healthy pregnant women. We adapted the Alternated Healthy Eating Index-2010 for pregnancy (AHEI-10P). The association between maternal diet and newborn nutritional status was investigated by multiple linear regression and logistic regression models. We applied three 24-h recalls during the second half of gestation. As the AHEI-10P score improved by 5 units, the birth weight and length increased (β = 74.8 ± 35.0 g and β = 0.3 ± 0.4 cm, respectively, p < 0.05). Similarly, the risk of low birth weight (LBW) and small for gestational age (SGA) decreased (OR: 0.47, 95%CI: 0.27–0.82 and OR: 0.55, 95%CI: 0.36–0.85, respectively). In women without preeclampsia and/or GDM, the risk of stunting decreased as the diet quality score increased (+5 units) (OR: 0.62, 95%IC: 0.40–0.96). A high-quality diet during pregnancy was associated with a higher newborn size and a reduced risk of LBW and SGA in this group of pregnant Mexican women.

Conclusions: A high-quality diet during pregnancy was associated with a higher newborn weight, length, and reduced risk of low birth weight and SGA. Women who did not develop preeclampsia and/or GDM also showed this association and had a lower risk of stunting. AHEI-10P is an alternative for evaluating diet quality in pregnant women, focusing on important nutrients for maternal and fetal health. More studies evaluating diet (quantity and quality) and its effects on newborn nutrition status in developing countries are necessary.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8227044/

Abstract

Background: Anxiety and depression can seriously undermine mental health and quality of life globally. The consumption of junk foods, including ultra-processed foods, fast foods, unhealthy snacks, and sugar-sweetened beverages, has been linked to mental health. The aim of this study is to use the published literature to evaluate how junk food consumption may be associated with mental health disorders in adults.

Methods: A systematic search was conducted up to July 2023 across international databases including PubMed/Medline, ISI Web of Science, Scopus, Cochrane, Google Scholar, and EMBASE. Data extraction and quality assessment were performed by two independent reviewers. Heterogeneity across studies was assessed using the I2 statistic and chi-square-based Q-test. A random/fixed effect meta-analysis was conducted to pool odds ratios (ORs) and hazard ratios (HRs).

Results: Of the 1745 retrieved articles, 17 studies with 159,885 participants were suitable for inclusion in the systematic review and meta-analysis (seven longitudinal, nine cross-sectional and one case-control studies). Quantitative synthesis based on cross-sectional studies showed that junk food consumption increases the odds of having stress and depression (OR = 1.15, 95% CI: 1.06 to 1.23). Moreover, pooling results of cohort studies showed that junk food consumption is associated with a 16% increment in the odds of developing mental health problems (OR = 1.16, 95% CI: 1.07 to 1.24).

Conclusion: Meta-analysis revealed that consumption of junk foods was associated with an increased hazard of developing depression. Increased consumption of junk food has heightened the odds of depression and psychological stress being experienced in adult populations.

https://pubmed.ncbi.nlm.nih.gov/38867156/

Abstract

Background: With the increasing prevalence of pregnant women adhering to a vegan diet, gaining insight into their nutritional intake and its association with maternal and fetal outcomes is essential to providing recommendations and developing guidelines for general practice.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of the available scientific literature in Medline, Embase, and Cochrane was conducted in January 2024.

Results: The titles and abstracts of 2211 unique articles were screened. Only six studies were eligible for inclusion and assessed for methodological quality using the (National Institutes of Health Study Quality (NIHSQ) Assessment Tool. The intake of protein and various micronutrients was significantly lower among vegan pregnant women compared to omnivorous women. Vitamin B12 supplements seemed sufficient in optimizing maternal and umbilical cord vitamin B12 levels amongst vegan mothers. Further, women on a vegan diet less often showed excessive pregnancy weight gain. However, children from women on a vegan diet had a significantly lower birth weight than those from women on an omnivorous diet.

Conclusion: So far, only a few studies, with a large diversity of (assessment of) outcomes and insufficient power, have been published on this topic, limiting our ability to make firm conclusions about the effects of a vegan diet during pregnancy on maternal and fetal outcomes.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11478456/

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And is that also why omega 3 supplements are more used compared to omega 6 supplements (I'm well aware that through the western diet people get enough of omega 6, but still).

I'm trying to understand this area better so I'd appreciate any input :)

How important is the omega 3 : omega 6 ratio? Should you be eating high omega 3 foods (chia, flax, walnuts, salmon, etc.) every day to balance out the omega 6? Will it harm your brain/heart/etc. health to eat way more omega 6 and only eat omega 3 rich foods once or twice a week, if ever?

I’m consciously increasing my protein intake

Im a 23 year old 5'8 142lb black male, I used to average about ~80-100 grams of protein a day. Trying to boost that to between 130-165 grams a day. I usually drink about 6L of water everyday, I work out, but lately I’ve been unable to consistently work out due to various life events and obligations so I’m just focusing on trying to eat clean.

How much fiber should I be eating to process this amount of protein? I try to go for at least 40-50 grams, but sometimes there isn’t enough and I have to settle for ~30 grams.

I've seen people on carnivore forums say that fiber is inherently bad for you because you don't digest it, but the typical advice is that we need fiber to be regular and also to feed our microbiome. I am very confused. How do people who eat zero plant material use the restroom? Do you really not need fiber? Can you eat too many vegetables (too much waste)?

Suppose we eat according to a recommended dietary pattern like USDA MyPlate, so deficiencies are not a concern. Is there any benefit to consuming a combination of mustard greens, cilantro, and spinach versus just mustard greens to fulfill the leafy greens requirement?

I've seen it argued that they provide different phytonutrients, but this implicitly assumes that the combination of phytonutrients would be better than just a higher dose from mustard greens alone. One could argue similarly for antinutrients.

The leafy greens are just to illustrate the point; I am broadly interested in whether there are theoretical or empirical arguments for diverse diets in the absence of nutritional concerns.

The most popular questions (e.g., which fats to avoid) are answered by innumerable dietary guidelines and position papers. At the next level, expert consensus is still readily available for less popular questions (e.g., protein intake for muscle building), but the sources are far fewer. However, for really esoteric questions (e.g., optimal protein intake for longevity or the healthiness of mycoprotein), it can be very difficult to find expert consensus. So if you have a question like that but are unable or unwilling to do the research yourself, how do you get an answer?