While atazanavir/ritonavir does reduce the lamotrigine plasma concentration, no adjustments to the recommended dose-escalation guidelines for LAMICTAL should be necessary solely based on the use of atazanavir/ritonavir. Dose escalation should follow the recommended guidelines for initiating adjunctive therapy with LAMICTAL based on concomitant AED or other concomitant medications (see Tables 1, 2, and 5). In patients already taking maintenance doses of LAMICTAL and not taking glucuronidation inducers, the dose of LAMICTAL may need to be increased if atazanavir/ritonavir is added, or decreased if atazanavir/ritonavir is discontinued [see CLINICAL PHARMACOLOGY ].
And, exacerbating these two age-related erosive events, some catabolites
of tryptophan can lead to the formation of mutagenic nitrosamines or
the activation of an immunosuppressive receptor (which is usually
triggered by toxicants such as xenobiotics), promoting carcinogenesis
(Mezrich, et al., 2010; Chung & Gadupudi, 2011).
The consumption of a supplement of tryptophan will likely nurture or augment these disastrous age-associated disease states, by raising injurious tryptophan derivatives (particularly in the presence of a vitamin B6 deficiency, an insufficiency of stomach acid, a magnesium deficit, and a vitamin B3 deficiency).
Furthermore, tryptophan side effects in regards to greater mortality were shown in animal experiments (., Catrina, et al., 2001) using melatonin, whereas the study authors cautioned:
“[...] melatonin had a deleterious effect on the survival rate raising the question whether it is correct to assume that the hormone shows lack of adverse reactions.” [emphasis added]
In regard to serotonin's involvement in the promotion of higher mortality, one of its anti-longevity effects is conceivably the reabsorption of phosphate (a pro-inflammatory chemical) by the kidneys since klotho, an anti-aging protein, facilitates the excretion of phosphate from the kidneys (Peat, Nov. 2012).
Since tryptophan, serotonin, and melatonin meddle with basic energy production in cells, and since metabolic efficiency and functionality decreases proportionally with aging (Fannin, et al., 1999; O'Toole, et al., 2010) due to various factors, it seems coherent in biological terms that these substances are less prevalent, thus less “essential” or needed, in older people, as a further decrease of an already suboptimal general metabolic working order will aggravate physiological function systematically, increase the risk for disease (as exemplified and foreshadowed with tryptophan side effects), promote the aging process, and explains the increased mortality related to the administration of these substances.
Several tryptophan side effects, such as tryptophan's carcinogenic activities, the deterioration of metabolic energy function, and the promotion of hypertension, can rather readily account for a greater death rate.