**5. Discussion**

*Visions of Cardiomyocyte - Fundamental Concepts of Heart Life and Disease*

Energy 0.319 −0.135 0.181 Protein 0.239 0.031 0.034 Animal protein 0.233 0.135 0.034 Vegetable protein 0.193 −0.081 0.152 Lipid 0.187 0.120 0.034 Animal lipid 0.188 0.154 0.094 Vegetable lipid 0.167 0.027 −0.066 Carbohydrate 0.188 −0.197 0.138 Na 0.128 0.033 −0.073 K 0.223 −0.015 0.137 Ca 0.099 0.263 −0.021 Mg 0.283 −0.003 0.143 Phosphorus 0.230 0.088 0.020 Iron 0.193 −0.120 0.112 Zinc 0.109 0.081 0.072 Copper 0.211 −0.066 0.163 Mn 0.422 −0.059 0.113 Retinol 0.307 −0.195 0.054 β-Carotene −0.001 −0.049 −0.005 Vit D 0.295 −0.001 −0.066 Tocopherol 0.167 −0.049 −0.004 Vit K 0.098 0.014 0.083 Vit B1 0.095 0.119 0.098 Vit B2 0.246 0.169 0.135 Niacine 0.320 −0.012 0.081 Vit B6 0.239 −0.036 0.129 Vit B12 0.353 −0.090 0.049 Folic acid 0.333 −0.120 0.080 Pantothenic acid 0.299 0.120 0.083 Vit C 0.214 −0.040 0.034 Saturated fatty acids 0.209 0.144 0.112 Monovalent fatty acids 0.156 0.126 −0.004 Multivalent fatty acids 0.179 0.024 −0.062 Cholesterol 0.221 −0.025 0.125 Soluble dietary fiber 0.133 −0.080 0.155 Insoluble dietary fiber 0.125 −0.047 0.076 Total dietary fiber 0.082 0.027 0.089 Salt 0.128 0.033 −0.073 Preference drinks 0.586\*\* −0.263 0.511\*

**Palmitelaidic Elaidic Linoelaidic**

**108**

**Table 3.**

*Correlations between foods intake and plasma levels of fatty acids.*

*Mean ± SD. \* p < 0.05. \*\*p < 0.01.*

Fatty acids are major components of blood vessels. So their changes exert tremendous impact to pathophysiology of cardiovascular system.

Epidemiological studies repeatedly showed that Japanese people had lower incidence of CVD, compared with American people [7]. As discussed below, kinds of intaken foods, life-styles, and genetics may contribute to such differences.

We thought the measurements of fatty acids composition in plasma may help to elucidate such differences between Japanese and American people.

We compared plasma levels of fatty acids between Japanese and American men over 50 years of age. We found, not surprisingly, that levels of EPA and DHA are higher in Japanese than American and that levels of arachidonic acid are lower in Japanese. Although both Japanese and American take meat, egg, and fish, fish has far more omega-3 fatty acids compared to eggs. When we eat larger amounts of omega-3 fatty acids such as DHA and EPA, omega-3 fatty acids are known to replace omega-6 fatty acids in cell membrane [36]. The omega-3 fatty acids are found predominantly in oily fish, whereas arachidonic acid (the major long chain omega-6 fatty acid) is contained in meats and eggs and can be synthesized (albeit very slowly) [37]. The differences between Japanese and US men in regard to the consumption of these types of foods can help explain these differences in blood levels [38]. The other major finding of this study was the lower levels of IP-TFA such as linoelaidic acid in Japanese vs. the US men.

Currently, CHD death rates in Japan are 3× lower for women and 4× lower for men (ages 35–74) compared with the US. Among 30 countries for which the American Heart Association provided CHD death rates in its 2017 Statistical Update [7], Japan had the second and third lowest rates (men and women, respectively) compared with the US. Sekikawa et al. [39] showed in 2014 that the calcification of the coronary artery was twice in American compared with Japanese men, but the calcification of Hawaiian Japanese was similar to that of people on the US mainland.

These results do not necessarily prove differences of CVD incidences between Japanese and American are due to foods and lifestyle. Since Japanese immigrants to the US have increased CHD mortality [40], although still lower US Whites, it appears that some genetic variabilities between American and Japanese must be responsible for this difference. However, the possibility that differences in dietary fatty acid patterns may contribute to this phenomenon is the subject of this report.

We found that the levels of the long-chain omega-3 fatty acids such as EPA and DHA were 2–3× higher in Japan vs. the US. The relationship of fish and dietary omega-3 fatty acids and cardiovascular disease (CVD) has been investigated in numerous studies and comprehensive reviews and recommendations exist. Still controversies exist. A recent meta-analysis of randomized trials with omega-3 fatty acids [41] did not find a statistically significant reduction in CVD mortality, but in these researches, some important factors were said to be ignored [42–44]. Other systematic reviews have reported mortality benefits for omega-3 fatty acids [45, 46], and omega-3 biomarker levels have been strongly associated with risk for fatal CHD in still other meta-analyses [47, 48]. Hence, higher omega-3 levels could at least partly explain the lower CHD risk in Japan.

We also found that IP-trans-fatty acid such as linoelaidic acid was lower in Japan than US. The reported intake of IP-TFA is 75% lower in Japan than in the US, again supporting the observed differences in biomarker levels. Circulating 18:2 trans-fatty acids was shown to be most adversely associated with total mortality, mainly due to the increased risk of CVD [23]. It was also positively associated with total mortality and CHD.

It may be surprising that TFA is not necessarily adverse for health. Some are beneficial for health. In a recent study from Germany, total trans-fatty acids in erythrocyte membranes were shown to be inversely associated with mortality, but this was mainly driven by the naturally occurring 16:1 trans (trans-palmitoleic acid) [49]. As to relationship between IP-TFA or SFA intakes and CHD mortality, excessive intakes of both had a greater impact on risk for CHD in the US compared with Japan, whereas insufficient intakes of omega-6 PUFAs had about the same impact on risk in both countries [50].

Our results also indicate that plasma levels of SFAs are higher in American than in Japanese. Saturated fatty acids are considered to be one of the dietary risk factors of CVD, primarily because these fats raise LDL-cholesterol levels. Many health and government organizations have recommended the reduction of intakes of SFA s to lower the incidence of CVD. Although this difference in SFA plasma levels may also be one of the reasons that Americans have a higher mortality rate for CVD than Japanese, plasma saturated (and monounsaturated) fatty acids are claimed to be relatively poor markers of dietary SFA (saturated fatty acid) intake [51].

Plasma fatty acid profiles in older men from Japan and US differed in many ways that are consistent with the lower rate of CHD in the former country. Efforts to lower TFA levels and increase EPA + DHA levels may help lower risk for CHD in the US, and current trends in Japan toward a more western diet [52] should be discouraged.

As to relationship between TFA or SFA intakes and CHD mortality, excessive intakes of both had a greater impact on risk for CHD in the US compared with Japan, whereas insufficient intakes of omega-6 PUFAs had about the same impact on risk in both countries [50]. As stated above, naturally occurring trans fats are consumed in smaller amounts (about 0.5% of total energy intake) in meats and dairy products from cows, sheep, and other ruminants; these trans fats are produced by the action of bacteria in the ruminant stomach [22]. Since trans-fatty acids are not used in foods in Japan, all the trans-fatty acids must come from meat or dairy products. We found that there was no relationship between various foods intake and plasma levels of trans-fatty acids in Japanese old men. Only intakes of preference drinks such as tea and coffee had significant relationship with plasma levels of palmitoelaidic acid and linoelaidic acid. These results seem to indicate that plasma levels of trans-fatty acids are not derived from foods but derived by intestinal microbes.

Human gut microbes are important in neural, endocrine, and immune communication with the host [53]. Communication is considered to be bidirectional. Mediators of microbiota-gut-brain communication affected by microbial metabolism include short-chain fatty acids, neurotransmitters such as serotonin, γ-aminobutyric acid (GABA), hormones such as cortisol, and immune system mediators such as quinolinic acid [51].

In conclusion, some of trans-fatty acids may be produced by hydrogenation of fatty acids by gut microbes.

#### **6. Conclusion**

We here report our results of comparison of plasma levels of fatty acids between healthy old men in Japan and the US.

The higher levels of DHA and EPA, along with the lower levels of the IP-TFAs, are consistent with the markedly lower risk for coronary heart disease in Japan vs. the US.

**111**

**Author details**

Akikazu Takada1

Tokyo, Japan

Medicine, Tokyo, Japan

\*, Fumiko Shimizu<sup>2</sup>

1 Hamamatsu University School of Medicine, Tokyo, Japan

\*Address all correspondence to: takadaa@mwd.biglobe.ne.jp

provided the original work is properly cited.

2 Faculty of Life and Environmental Sciences, Showa Women's University,

3 Division of Cardiology, Department of Medicine, Showa University School of

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

and Shinji Koba<sup>3</sup>

*Roles of Trans and ω Fatty Acids in Health; Special References to Their Differences…*

old men except for preference drinks such as tea or coffee.

of CVD, primarily because these fats raise LDL-cholesterol levels.

Various foods intake may not affect plasma levels of trans-fatty acids in Japanese

The higher levels of DHA and EPA, along with the lower levels of the IP-TFAs, are consistent with the markedly lower risk for coronary heart disease in Japan vs.

Our results also indicate that plasma levels of SFAs are higher in American than in Japanese. Saturated fatty acids are considered to be one of the dietary risk factors

Experiments were designed and performed by all of the authors. AT and WSH wrote the manuscript. Statistical analyses were done by FS. All authors read the manuscript and approved the final version. All the authors take responsibility for

*DOI: http://dx.doi.org/10.5772/intechopen.89551*

the US.

**Acknowledgements**

the final content.

*Roles of Trans and ω Fatty Acids in Health; Special References to Their Differences… DOI: http://dx.doi.org/10.5772/intechopen.89551*

Various foods intake may not affect plasma levels of trans-fatty acids in Japanese old men except for preference drinks such as tea or coffee.

The higher levels of DHA and EPA, along with the lower levels of the IP-TFAs, are consistent with the markedly lower risk for coronary heart disease in Japan vs. the US.

Our results also indicate that plasma levels of SFAs are higher in American than in Japanese. Saturated fatty acids are considered to be one of the dietary risk factors of CVD, primarily because these fats raise LDL-cholesterol levels.
